Persistence and effectiveness of guselkumab treatment in patients with moderate-to-severe plaque psoriasis in a non-interventional real-world setting: The SPRING study.

BACKGROUND: Guselkumab is a monoclonal antibody that blocks the IL-23 pathway with proven efficacy and tolerability in the treatment of moderate-to-severe plaque psoriasis. OBJECTIVES: To assess the persistence, effectiveness and safety of guselkumab in patients with moderate-to-severe psoriasis in real clinical practice in Spain. METHODS: SPRING was a Phase IV, retrospective and non-interventional study analysing patients with moderate-to-severe plaque psoriasis who had initiated guselkumab under clinical practice conditions at least 12 months before inclusion in the study. The primary endpoint was persistence (non-persistence: discontinuation or interruption ≥90 days). Effectiveness was assessed using the Psoriasis Area Severity Index (PASI) and Investigator Global Assessment (IGA). Dermatology Life Quality Index (DLQI) and safety were also evaluated. RESULTS: A total of 284 patients were included between September 2020 and June 2021. The 1-year probability of persistence was 89.6% (86.1%-93.3%). The 1-year probability of persistence was also calculated according to prior biologic treatment, being 90.3% for biologic-naïve patients and 89.5% for patients who received one or more biologic therapies before guselkumab. Additionally, patients were also classified based on the frequency of the administration of guselkumab treatment; the 1-year probability of persistence was 91.9% in patients receiving guselkumab according to the Summary of Product Characteristics and 89.3% in patients with lengthened intervals of administration. After 1 year, PASI 90 was achieved by 56.4% of patients, IGA 0/1 response and BSA <3% were achieved by 65.5% and 77.8% of patients, respectively, and 65.8% achieved a minimal clinically significant difference (>4-point reduction) in the DLQI score at 1 year. Twenty-six adverse reactions (4 of them serious) were reported in 16 patients. CONCLUSIONS: This study suggests that guselkumab has high persistence in real clinical practice in Spain, independently of the previous biologic treatments and changes in the frequency of treatment. Effectiveness and safety are consistent with previously published data.

Beaming in the Charcot foot: A case series with 12-month minimum follow-up.

BACKGROUND: Charcot neuropathic arthropathy is a progressive degeneration of the weightbearing joints of the foot induced by denervation and disturbance of sensorial perception. This entity clinically behaves as a destructive fast-progressive arthropathy, resulting in loss of independent walking and often requiring amputation of the leg. This study analyzes our experience with midfoot realignment arthrodesis and stabilization by intramedullary beaming in patients with Charcot diabetic foot as a limb-sparing procedure. METHODS: Patients with Charcot foot treated in our Foot and Ankle unit between January 2018 and December 2019 were analyzed. In all of the patients beaming technique was performed: open reduction and stabilization by a midfoot medial fusion beam and a lateral fusion bolt. Demographical, clinical and radiological pre and post-surgery data were assessed. The primary outcome measure was defined as an autonomous ambulation through an ulcer-free plantigrade foot. A minimum follow-up of 12 months was performed. RESULTS: A total of 5 patients were treated. Median age 64 years, mean follow-up 25 months (12-31). An ulcer-free plantigrade foot was obtained in 80% of the patients. Complications were observed in 80% of patients: 1 deep infection, 2 hardware failure, 3 Charcot foot progression. Rate of reoperation 40%, including 1 amputation. Significant improvement in all radiographic angles was observed. CONCLUSION: Beaming the medial and lateral columns of the foot in patients with Charcot foot enabled the restoration of a functional plantigrade foot and an ulcer-free autonomous ambulation, despite a relatively high complication rate. LEVEL OF EVIDENCE: IV, prospective case series.

Ventilator-associated pneumonia and bloodstream infections in intensive care unit cancer patients: a retrospective 12-year study on 3388 prospectively monitored patients.

PURPOSE: Some publications suggest high rates of healthcare-associated infections (HAIs) and of nosocomial pneumonia portending a poor prognosis in ICU cancer patients. A better understanding of the epidemiology of HAIs in these patients is needed. METHODS: A retrospective analysis of all the patients hospitalized for ≥ 48 h during a 12-year period in the 12-bed ICU of the Gustave Roussy hospital, monitored prospectively for ventilator-associated pneumonia (VAP) and bloodstream infection (BSI) and for use of medical devices. RESULTS: During 3388 first stays in the ICU, 198 cases of VAP and 103 primary, 213 secondary, and 77 catheter-related BSIs were recorded. The VAP rate was 24.5/1000 ventilator days (95% confidence interval [CI] 21.2-28.0); the catheter-related BSI rate was 2.3/1000 catheter days (95% CI 1.8-2.8). The cumulative incidence during the first 25 days of exposure was 58.8% (95% CI 49.1-66.6%) for VAP, 8.9% (95% CI, 6.2-11.5%) for primary, 15.1% (95% CI 11.6-18.5%) for secondary and 5.0% (95% CI 3.2-6.8%) for catheter-related BSIs. VAP or BSIs were not associated with a higher risk of ICU mortality. CONCLUSIONS: This is the first study to report HAI rates in a large cohort of critically ill cancer patients. Although both the incidence of VAP and the rate of BSI are higher than in general ICU populations, this does not impact patient outcomes. The occurrence of device-associated infections is essentially due to severe medical conditions in patients and to the characteristics of malignancy.

On the turn-inducing properties of asparagine: the structuring role of the amide side chain, from isolated model peptides to crystallized proteins.

Asparagine (Asn) is a powerful turn-inducer residue, with a large propensity to occupy the second position in the central region of ß-turns of proteins. The present work aims at investigating the role of a local anchoring between the Asn side chain and the main chain in this remarkable property. For this purpose, the H-bonding patterns of an asparagine residue in an isolated protein chain fragment forming a γ- or a ß-turn have been determined using IR/UV double resonance gas phase spectroscopy on laser-desorbed, jet-cooled short models in conjunction with relevant quantum chemistry calculations. These gas phase data provide evidence for an original double anchoring linking the Asn primary amide side chain (SC), which adopts a gauche+ rotameric form, to its main chain (MC) local environment. From both IR spectroscopic evidence (H-bond induced red shifts) and quantum chemistry, Asn SC is found to behave as a stronger H-bond acceptor than donor, resulting in stronger MC→SC H-bonds than SC→MC ones. These gas phase structural data, relevant to a hydrophobic environment, have been used as a reference to assess the anchoring taking place in high resolution crystallized proteins of the Protein Data Bank. This approach reveals that, when the SC adopts a gauche+ orientation, the stronger MC→SC bonds are preserved in many cases whereas the SC→MC bonds are always disrupted, in qualitative agreement with the gas phase ranking of these interactions. Most interestingly, when Asn occupies the second position of central part of a ß-turn (i.e., the very turn-inducer position), the MC→SC H-bonds are also disrupted and replaced by a water-mediated SC to MC anchoring. Owing to the specific features of the hydrated Asn side chain, we propose that it could be a turn precursor structure, able to facilitate turn formation in the early events of the folding process.

Colorectal cancer (CRC) monitoring by 6-monthly 18FDG-PET/CT: an open-label multicentre randomised trial.

Background: [18F]2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18FDG-PET/CT) has high sensitivity for detecting recurrences of colorectal cancer (CRC). Our objective was to determine whether adding routine 6-monthly 18FDG-PET/CT to our usual monitoring strategy improved patient outcomes and to assess the effect on costs. Patients and methods: In this open-label multicentre trial, patients in remission of CRC (stage II perforated, stage III, or stage IV) after curative surgery were randomly assigned (1 : 1) to usual monitoring alone (3-monthly physical and tumour marker assays, 6-monthly liver ultrasound and chest radiograph, and 6-monthly whole-body computed tomography) or with 6-monthly 18FDG-PET/CT, for 3 years. A multidisciplinary committee reviewed each patient's data every 3 months and classified the recurrence status as yes/no/doubtful. Recurrences were treated with curative surgery alone if feasible and with chemotherapy otherwise. The primary end point was treatment failure defined as unresectable recurrence or death. Relative risks were estimated, and survival was analysed using the Kaplan-Meier method, log-rank test, and Cox models. Direct costs were compared. Results: Of the 239 enrolled patients, 120 were in the intervention arm and 119 in the control arm. The failure rate was 29.2% (31 unresectable recurrences and 4 deaths) in the intervention group and 23.7% (27 unresectable recurrences and 1 death) in the control group (relative risk = 1.23; 95% confidence interval, 0.80-1.88; P = 0.34). The multivariate analysis also showed no significant difference (hazards ratio, 1.33; 95% confidence interval, 0.8-2.19; P = 0.27). Median time to diagnosis of unresectable recurrence (months) was significantly shorter in the intervention group [7 (3-20) versus 14.3 (7.3-27), P = 0.016]. Mean cost/patient was higher in the intervention group (18 192 ± 27 679 € versus 11 131 ± 13 €, P < 0.033). Conclusion: 18FDG-PET/CT, when added every 6 months, increased costs without decreasing treatment failure rates in patients in remission of CRC. The control group had very close follow-up, and any additional improvement (if present) would be small and hard to detect. ClinicalTrials.gov identifier: NCT00624260.

Desmontaje por efecto cut-out en el enclavado de fracturas pertrocantéreas de fémur: ¿cuál es el tratamiento de rescate de elección? / Removal due to cut-out effect in pertrochanteric femoral fractures: what is the rescue treatment of choice?

Objetivo. Comparar los resultados funcionales de las distintas opciones terapéuticas, y analizar los factores técnicos asociados al cut-out. Material y método. Estudio de cohortes retrospectivo de 56 pacientes diagnosticados de cut-out entre 2000-2010, divididos en dos grupos en función del tratamiento de rescate: artroplastia frente a conservar la cabeza femoral (alternativo). Se analizaron datos demográficos, características de la fractura y osteosíntesis, tip to apex distance (TAD), seguimiento, complicaciones y capacidad funcional final. Resultados. Grupo artroplastia 36 pacientes (64,28%) y 20 (35,72%) grupo alternativo. Comparables en parámetros demográficos, comorbilidades, patrón de fractura y características de la osteosíntesis. Se observó poca variabilidad interobservador (k = 0,83; IC 95%: 0,78-0,88) en el análisis radiográfico; con un TAD medio de 28,66 mm (p = 0,01) y un déficit de reducción en el 39,3% (p = 0,001). La mediana de cut-out fue de 60 días (artroplastia 90, alternativo 18; p = 0,001). Seguimiento mínimo 12 meses, con tasa de complicaciones similar en ambos grupos (p = 0,16) y de reintervención del 3,57% (p = 0,01). La capacidad funcional final fue mayor en el grupo de artroplastia (p = 0,004). Conclusión. El tratamiento de rescate con artroplastia ofrece mejores resultados funcionales, considerándolo el tratamiento de elección en pacientes ancianos, aunque la tasa de reintervención es mayor. Recomendamos nuevo enclavado antes que artroplastia en los casos de cut-out temprano (< 4 semanas) en aquellos casos que se mantenga la integridad de la cabeza femoral. Un déficit de reducción de la fractura es el principal factor predictor de fallo a corto plazo; un TAD por encima de 20 mm lo es a medio-largo plazo (AU)

Objective. The goal of the study was to compare functional results in different treament options in cutting-out, and analize factors associated to failure. Material and methods. Retrospective cohort study in 56 patients diagnosed with cutting-out between 2000-2010. Groups were based on rescue treatment: arthroplasty versus alternative treatment. Demographics, fracture characteristics, osteosynthesis, tip to apex distance (TAD), follow-up, complications, and final functional capacity were analyzed. Results. Rescue treatment: 36 (64.28%) hip replacement (arthroplasty group), and 20 (35.72%) alternative treatment preserving femoral head (alternative group). Groups comparable on demographic parameters, fracture pattern and osteosynthesis characteristics. Radiography analysis: low inter-observer variability (k = 0.83, 95% CI 0.78-0.88), mean TAD 28.66 mm (arthroplasty group 32.9 mm, 21.5 mm control group; p = 0.01), insufficient fracture reduction 39.3% (p = 0.001). Cutting-out diagnosis median 60 days (arthroplasty group 90 days, 18 days alternative group; p = 0.001). Follow up at least 12 months from rescue treatment. Similar complications rate in both groups (p = 0.16). Re-operation rate 3.57% (11.7% arthroplasty group, alternative group 0%; p = 0.01). Better final functional capacity in arthroplasty group (p = 0.004). Discussion. Hip arthroplasty offers better results, being considered the gold standard in geriatric patients, although re-operation rate is higher. We recommend new nailing before arthroplasty in early failure (4 weeks) in patients with femoral head integrity. An insufficient fracture reduction is the main short term factor predicting failure; and TAD higher than 20 mm is a middle-long term one (AU)

[Removal due to cut-out effect in pertrochanteric femoral fractures: what is the rescue treatment of choice?]. / Desmontaje por efecto cut-out en el enclavado de fracturas pertrocantéreas de fémur: ¿cuál es el tratamiento de rescate de elección?

OBJECTIVE: The goal of the study was to compare functional results in different treament options in cutting-out, and analize factors associated to failure. MATERIAL AND METHODS: Retrospective cohort study in 56 patients diagnosed with cutting-out between 2000-2010. Groups were based on rescue treatment: arthroplasty versus alternative treatment. Demographics, fracture characteristics, osteosynthesis, tip to apex distance (TAD), follow-up, complications, and final functional capacity were analyzed. RESULTS: Rescue treatment: 36 (64.28%) hip replacement (arthroplasty group), and 20 (35.72%) alternative treatment preserving femoral head (alternative group). Groups comparable on demographic parameters, fracture pattern and osteosynthesis characteristics. Radiography analysis: low inter-observer variability (k=0.83, 95% CI 0.78-0.88), mean TAD 28.66mm (arthroplasty group 32.9mm, 21.5mm control group; p=0.01), insufficient fracture reduction 39.3% (p=0.001). Cutting-out diagnosis median 60 days (arthroplasty group 90 days, 18 days alternative group; p=0.001). Follow up at least 12 months from rescue treatment. Similar complications rate in both groups (p=0.16). Re-operation rate 3.57% (11.7% arthroplasty group, alternative group 0%; p=0.01). Better final functional capacity in arthroplasty group (p=0.004). DISCUSSION: Hip arthroplasty offers better results, being considered the gold standard in geriatric patients, although re-operation rate is higher. We recommend new nailing before arthroplasty in early failure (4 weeks) in patients with femoral head integrity. An insufficient fracture reduction is the main short term factor predicting failure; and TAD higher than 20mm is a middle-long term one.

Unraveling non-covalent interactions within flexible biomolecules: from electron density topology to gas phase spectroscopy.

The NCI (Non-Covalent Interactions) method, a recently-developed theoretical strategy to visualize weak non-covalent interactions from the topological analysis of the electron density and of its reduced gradient, is applied in the present paper to document intra- and inter-molecular interactions in flexible molecules and systems of biological interest in combination with IR spectroscopy. We first describe the conditions of application of the NCI method to the specific case of intramolecular interactions. Then we apply it to a series of stable conformations of isolated molecules as an interpretative technique to decipher the different physical interactions at play in these systems. Examples are chosen among neutral molecular systems exhibiting a large diversity of interactions, for which an extensive spectroscopic characterization under gas-phase isolation conditions has been obtained using state-of-the-art conformer-specific experimental techniques. The interactions presently documented range from weak intra-molecular H-bonds in simple amino-alcohols, to more complex patterns, with interactions of various strengths in model peptides, as well as in chiral bimolecular systems, where invaluable hints for the understanding of chiral recognition are revealed. We also provide a detailed technical appendix, which discusses the choices of cut-offs as well as the applicability of the NCI analysis to specific constrained systems, where local effects require attention. Finally, the NCI technique provides IR spectroscopists with an elegant visualization of the interactions that potentially impact their vibrational probes, namely the OH and NH stretching motions. This contribution illustrates the power and the conditions of use of the NCI technique, with the aim of providing an easy tool for all chemists, experimentalists and theoreticians, for the visualization and characterization of the interactions shaping complex molecular systems.

[Autologous concentrated bone marrow graft in the treatment of femoral head avascular necrosis: clinical outcome after two years of follow up in a non-controlled prospective study]. / Implante de concentrado de médula ósea autógeno en el tratamiento de la necrosis isquémica de cabeza femoral: evolución clínica al segundo año de seguimiento de un estudio prospectivo no controlado.

OBJECTIVE: To assess the efficacy of implanting concentrated bone marrow rich in mesenchymal stem cells (MSC) for the treatment of femoral head avascular necrosis (AVN) to prevent or delay total hip replacement (THR). MATERIAL AND METHODS: A single-centre, prospective, non-controlled clinical study was conducted on patients with a diagnosis of AVN. The parameters assessed were, patient demographics, Harris Hip Score (HHS), imaging test (X-ray and NMR), and staging using the Arlet-Ficat scale. The patients were followed up for 1, 6, 12 and 24 months. The bone marrow was aspirated from the iliac crest, concentrated with the Harvest SmartPReP 2 system, and infused into the necrotic area by means of core decompression. RESULTS: A total of 22 hips in 17 patients were recruited between the years 2006 to 2012, with a minimum follow-up of 2 years. A mean of 119.5 mL of aspirate was extracted, with 15.25 ml of MSC being implanted. During the first 2 years of the infusion, 5 hips (24.7%) required THR, with no differences in the baseline Arlet-Ficat stage, and 4 of these (80%) had femoral head involvement equal to or higher than 30%. A significant increase of 14.27 (P=.026) in the HHS and a 0.98 (P=.089) decrease in the VAS was observed two years after the infusion in the remaining 17 hips. The results suggest that the infusion of concentrated bone marrow rich in MSC, combined with surgical decompression of the nucleus, improves hip function (HHS), and avoids THR in 75.3% of patients with AVN treated during the first 2 years.

Implante de concentrado de médula ósea autógeno en el tratamiento de la necrosis isquémica de cabeza femoral: evolución clínica al segundo año de seguimiento de un estudio prospectivo no controlado / Autologous concentrated bone marrow graft in the treatment of femoral head avascular necrosis: Clinical outcome after two years of follow up in a non-controlled prospective study

Objetivo. Evaluar la utilidad del aporte de concentrado de médula ósea rico en células troncales mesenquimales (MSC) como tratamiento de la necrosis avascular de cabeza femoral (NAV) para evitar o retrasar la artroplastia total de cadera (ATC). Material y métodos. Estudio clínico unicéntrico, prospectivo, no controlado, de pacientes con diagnóstico de NAV. Evaluación de parámetros demográficos, Harris Hip Score (HHS), pruebas de imagen (radiografía y RMN); estadificación mediante escala de Arlet-Ficat. Seguimiento a 1, 6, 12 y 24 meses. Aspirado de médula ósea de cresta ilíaca, concentrado con sistema Harvest SmartPReP 2, e infusión en zona de necrosis mediante forages. Resultados. Veintidós caderas en 17 pacientes fueron reclutados entre los años 2006-2012, seguimiento mínimo 2 años. Extracción media de 119,5ml de aspirado, implantándose 15,25ml de concentrado de MSC. Durante los primeros 2 años de la infusión 5 caderas (24,7%) precisaron ATC, sin diferencias en estadio de Ficat basal, y 4 (80%) de ellas presentaban afectación de cabeza femoral igual o superior al 30%. En las 17 caderas restantes, se observó a los 2 años de la infusión un aumento significativo del HHS (14,27) (p=0,026) y disminución del dolor (0,98) en la EVA (p=0,089). Nuestros resultados sugieren que la infusión de concentrado de médula ósea rico en MSC asociado a descompresión quirúrgica del núcleo mejora significativamente la funcionalidad de la cadera (HHS) y evita la ATC en el 75,3% de los pacientes con NAV tratados durante los primeros 2 años (AU)

Objective. To assess the efficacy of implanting concentrated bone marrow rich in mesenchymal stem cells (MSC) for the treatment of femoral head avascular necrosis (AVN) to prevent or delay total hip replacement (THR). Material and methods. A single-centre, prospective, non-controlled clinical study was conducted on patients with a diagnosis of AVN. The parameters assessed were, patient demographics, Harris Hip Score (HHS), imaging test (X-ray and NMR), and staging using the Arlet-Ficat scale. The patients were followed up for 1, 6, 12 and 24 months. The bone marrow was aspirated from the iliac crest, concentrated with the Harvest SmartPReP 2 system, and infused into the necrotic area by means of core decompression. Results. A total of 22 hips in 17 patients were recruited between the years 2006 to 2012, with a minimum follow-up of 2 years. A mean of 119.5mL of aspirate was extracted, with 15.25ml of MSC being implanted. During the first 2 years of the infusion, 5 hips (24.7%) required THR, with no differences in the baseline Arlet-Ficat stage, and 4 of these (80%) had femoral head involvement equal to or higher than 30%. A significant increase of 14.27 (P=.026) in the HHS and a 0.98 (P=.089) decrease in the VAS was observed two years after the infusion in the remaining 17 hips. The results suggest that the infusion of concentrated bone marrow rich in MSC, combined with surgical decompression of the nucleus, improves hip function (HHS), and avoids THR in 75.3% of patients with AVN treated during the first 2 years (AU)

Use of the Threshold of Toxicological Concern (TTC) approach for deriving target values for drinking water contaminants.

Ongoing pollution and improving analytical techniques reveal more and more anthropogenic substances in drinking water sources, and incidentally in treated water as well. In fact, complete absence of any trace pollutant in treated drinking water is an illusion as current analytical techniques are capable of detecting very low concentrations. Most of the substances detected lack toxicity data to derive safe levels and have not yet been regulated. Although the concentrations in treated water usually do not have adverse health effects, their presence is still undesired because of customer perception. This leads to the question how sensitive analytical methods need to become for water quality screening, at what levels water suppliers need to take action and how effective treatment methods need to be designed to remove contaminants sufficiently. Therefore, in the Netherlands a clear and consistent approach called 'Drinking Water Quality for the 21st century (Q21)' has been developed within the joint research program of the drinking water companies. Target values for anthropogenic drinking water contaminants were derived by using the recently introduced Threshold of Toxicological Concern (TTC) approach. The target values for individual genotoxic and steroid endocrine chemicals were set at 0.01 µg/L. For all other organic chemicals the target values were set at 0.1 µg/L. The target value for the total sum of genotoxic chemicals, the total sum of steroid hormones and the total sum of all other organic compounds were set at 0.01, 0.01 and 1.0 µg/L, respectively. The Dutch Q21 approach is further supplemented by the standstill-principle and effect-directed testing. The approach is helpful in defining the goals and limits of future treatment process designs and of analytical methods to further improve and ensure the quality of drinking water, without going to unnecessary extents.

Gas-phase folding of a two-residue model peptide chain: on the importance of an interplay between experiment and theory.

In order to assess the ability of theory to describe properly the dispersive interactions that are ubiquitous in peptide and protein systems, an isolated short peptide chain has been studied using both gas-phase laser spectroscopy and quantum chemistry. The experimentally observed coexistence of an extended form and a folded form in the supersonic expansion was found to result from comparable Gibbs free energies for the two species under the high-temperature conditions (< or = 320 K) resulting from the laser desorption technique used to vaporize the molecules. These data have been compared to results obtained using a series of quantum chemistry methods, including DFT, DFT-D, and post-Hartree-Fock methods, which give rise to a wide range of relative stabilities predicted for these two forms. The experimental observation was best reproduced by an empirically dispersion-corrected functional (B97-D) and a hybrid functional with a significant Hartree-Fock exchange term (M06-2X). In contrast, the popular post-Hartree-Fock method MP2, which is often used for benchmarking these systems, had to be discarded because of a very large basis-set superposition error. The applicability of the atomic counterpoise correction (ACP) is also discussed. This work also introduces the mandatory theoretical examination of experimental abundances. DeltaH(0 K) predictions are clearly not sufficient for discussion of folding, as the conformation inversion temperature is crucial to the conformation determination and requires taking into account thermodynamical corrections (DeltaG) in order to computationally isolate the most stable conformation.

Development of a common priority list of pharmaceuticals relevant for the water cycle.

Pharmaceutically active compounds (PhACs), including prescription drugs, over-the-counter medications, drugs used in hospitals and veterinary drugs, have been found throughout the water cycle. A desk study was initiated by the Global Water Research Coalition to consolidate a uniform selection of such compounds in order to judge risks of PhACs for the water cycle. By identifying major existing prioritization efforts and evaluating the criteria they use, this study yields a representative and qualitative profile ('umbrella view') of priority pharmaceuticals based on an extensive set of criteria. This can then be used for further studies on analytical methods, occurrence, treatability and potential risks associated with exposure to PhACs in water supply, identifying compounds most likely to be encountered and that may have significant impact on human health. For practical reasons, the present study excludes veterinary drugs. The pragmatic approach adopted provides an efficient tool to manage risks related to pharmaceuticals and provides assistance for selecting compounds for future studies.

Estimation of the consumption of cold tap water for microbiological risk assessment: an overview of studies and statistical analysis of data.

The volume of cold tap water consumed is an essential element in quantitative microbial risk assessment. This paper presents a review of tap water consumption studies. Study designs were evaluated and statistical distributions were fitted to water consumption data from The Netherlands, Great Britain, Germany and Australia. We conclude that the diary is to be preferred for collecting water consumption data. If a diary is not feasible, a 24 h recall would be the best alternative, preferably repeated at least once. From the studies evaluated, the mean daily consumption varies from 0.10 L to 1.55 L. No conclusions could be drawn regarding the effects of season, age and gender on tap water consumption. Physical activity, yearly income and perceived health status were reported to influence water consumption. Comparison of the different statistical probability distribution functions of the datasets demonstrated that the Poisson distribution performed better than the lognormal distribution as suggested by Roseberry and Burmaster. For quantitative microbiological risk assessment (QMRA) it is recommended to use country-specific consumption data and statistical distributions, if available. If no country specific data are available we recommend to use the Australian distribution data from the Melbourne diary study (Poisson, lambda=3.49 glasses/d) as a conservative estimate.

Intramolecular recognition in a jet-cooled short peptide chain: gamma-turn helicity probed by a neighbouring residue.

gamma-Turn, the shortest secondary structure of peptides, exists as two helical forms gamma(l) and gamma(d) of opposite handedness. The present gas phase study of capped l-Phe-Xxx peptides (Xxx = l-Ala, d-Ala or Aib: aminoisobutyric acid) provides a unique example of intramolecular chiral recognition of the gamma-turn helicity on Ala or Aib by the neighbouring residue Phe within the chain. With the chiral l- or d-Ala residues, the presence of a side-chain operates a discrimination between the two helical forms: one of them is widely favoured over the other (gamma(l) or gamma(d), respectively). This enables us to validate and calibrate the recognition capabilities of the nearby l-Phe residue. The discriminating interactions have been precisely characterized from their spectroscopic UV and IR signatures and identified by comparison with quantum chemistry calculations. Then, in the case of the non-chiral residue Aib, the two helical forms of the gamma-turn, which are simultaneously observed in the jet, have been discriminated and assigned by comparison with the chiral residues. The relative abundances of the diastereomeric forms l-Phe-Aib(gamma(l)) and l-Phe-Aib(gamma(d)) enable us to determine the most efficient recognition configuration.

Posible validez de medicamentos termolábiles fuera de las condiciones de conservación recomendadas por el fabricante / No disponible

El farmacéutico de hospital, según Ley 25/1990, de 20 de diciembre del Medicamento, debe garantizar la correcta conservación de los medicamentos tanto en el servicio de farmacia comoen los stocks del hospital. El almacenado y conservación de los medicamentos termolábiles en las condiciones establecidas por el fabricante, garantiza la estabilidad y condiciones óptimas de utilización hasta la fecha de caducidad. La rotura de la cadena de frío puede condicionar significativamente la actividad y toxicidad de estos medicamentos. El farmacéutico debe tomar decisiones rápidas en situaciones donde se haya producido alguna eventualidad en la cadena del frío, de ahí la importancia de disponer de datos actualizados de su estabilidad a temperaturas distintas a las recomendadas. Se ha realizado una revisión de la información disponible sobre estabilidad de los medicamentos que requieren conservación en frigorífico de uso más frecuente en el medio hospitalario (AU)

Hospital pharmacists, according to the Ley del Medicamento25/1990 of 20th December, should ensure appropriate drug preservation within the Pharmacy Department and in hospital stocks.The storage and preservation of thermolabile drugs according to manufacturer recommendations guarantees stability and optimaluse conditions until the expiry date. Cold chain disruption may significantly affect the activity and toxicity of these drugs. Pharmacists should make quick decisions in case of cold chain-relatedevents, hence the relevance of up-to-date information on stability under temperatures differing from those recommended. A review of the information available on the stability of drugs commonly used in the hospital setting that require a fridge for storage has been carried out (AU)

Spectroscopic studies of enantiomeric discrimination in jet-cooled chiral complexes.

Van der Waals complexes formed between chiral molecules in the isolated gas phase were studied by combining supersonic expansion techniques with laser spectroscopy. The weakly bound diastereoisomers formed between a chiral secondary alcohol, butan-2-ol, and a chiral aromatic derivative such as 2-naphthyl-1-ethanol or 1-phenylethanol used as a resolving agent were discriminated on the basis of the spectral shifts of the UV S(0)-S(1) transition of the chromophore. Ground-state depletion spectroscopy (hole burning) has shown that, while only one structure was detected for the 1-phenylethanol/butan-2-ol homochiral complex, the heterochiral complex is trapped in the jet under two different conformations. Two isomers have also been shown for each diastereoisomeric pair of the 2-naphthyl-1-ethanol/butan-2-ol complexes. Using a semiempirical potential model, these isomeric forms were related to calculated structures which exhibit a folded or extended geometry depending on the solvent conformation (anti or gauche). The relative binding energy of the complexes involving R-1-phenylethanol and R- or S-butan-2-ol were obtained from fragmentation threshold measurements following two-color photoionization. Comparison of the diastereoisomers exhibiting a similar spectral signature shows that the homochiral pair is more stable than the heterochiral one by about 0.7 kcal/mol. The fragmentation threshold has been shown to depend on the jet-cooled isomer and this result addresses the role of conformational control in enantioselective interactions.

[Neurofibroma of the lower lip]. / Neurofibroma de labio inferior.

Reporting a nervous tumor diagnosed as Neurofibroma, which owing to its localisation, on the lower lip, and its possible origin, from a salivary gland, should be considered an extraordinary rarity. The AA, make a bibliographic review of the commonest sites of the growth, the histological description and consider some possible differential diagnosis with special emphasis to the schwannoma and the Recklinghausen's disease.

[The action of 5-fluorouracil in DMH-induced carcinogenesis in rats]. / Acción del 5-fluorouracilo en la carcinogénesis inducida con DMH en ratas.

An experimental model to observe the action of 5-fluorouracil on rats with DMH-induced cancer of colon was designed. Ten Wistar rats were injected weekly with 25 subcutaneous doses (21 mg/kg) of DMH, and another ten, coinciding with the last 10 doses of the former, received intraperitoneally 10 mg/kg of the cytostatic agent. The animals were sacrificed 7 days after the last injection and samples of the colon processed by the "Swiss roll" technique. Differences in the weight of the animals and in the localization, size and macro and microscopic type of the tumours encountered, as well as the localization and grade of the dysplasias are studied.

Submucosal plexus of terminal ileum: a study of the cholinergic and noradrenergic nerves in rats with streptozotocin-induced diabetes.

In order to study the type and degree of the alterations in the innervation of the intestine in experimental diabetes, a histochemical study on the cholinergic and noradrenergic nerves of the submucosal plexus of terminal ileum from rats with streptozotocin-induced diabetes was performed. The results obtained suggest that the diabetic animals keep the cholinergic activity undamaged 20 weeks after the induction of the illness, while the number of the catecholaminergic nerves appears to be markedly reduced.